Deep cervical lymph node volume decreases following B-cell depletion therapy

Abstract

The deep cervical lymph nodes (dCLNs) are sites of immune presentation and B-cell maturation from the brain, and potentially involved in mechanisms of neuroinflammation. We hypothesized a reduction in dCLN volume following B-cell depletion therapy. In a retrospective cohort, we segmented bilateral dCLN from T2-FLAIR MRI at "prebaseline," "baseline," and "post-B-cell depletion" timepoints. Using a multivariable mixed-effect regression model, we find no changes in dCLN volumes between prebaseline and baseline timepoints (p > 0.05), but a significant decrease of 158 mm³ following ocrelizumab infusion (t = -3.3, p = 0.005). Baseline use of a disease-modifying therapy was also significantly associated with a smaller dCLN volume and attenuated the effects of B-cell depletion. These results are congruent with therapeutic mechanisms, although other alternative explanations for reductions in dCLN volumes cannot be ruled out based on this data. Deep CLN represent potential imaging biomarkers of pharmacological or clinical utility and warrant further investigation.

Keywords: B-cell depletion; MRI; Multiple sclerosis; cervical lymph node.

Figure 1.

Effects of ocrelizumab on deep cervical lymph node volume. Longitudinally aligned T2-FLAIR MRI scans reformatted to the coronal plane. The largest jugulodigastric lymph node on each side of the neck (here showing the left) was segmented using a threshold-based approach and depicted in the zoomed-in portion. The reduction in cervical lymph node (CLN) size is apparent at timepoint T1.

Figure 2.

“Spaghetti” plot showing cervical lymph node volumes in the subcohort with three timepoint assessments, in relation to B-cell depletion therapy (BCDT). Significance values are derived from a multivariable mixed-effect model adjusting for age, sex, and lymph node laterality with a patient-specific random effect.